Comparing GLP-1 Medications: Semaglutide vs Tirzepatide vs Retatrutide

Understanding the differences between these medications can help you make an informed decision about which option might be best for your weight loss journey.

Quick Comparison Table

Feature	Semaglutide	Tirzepatide	Retatrutide
Mechanism	GLP-1 agonist	GLP-1 + GIP dual agonist	GLP-1 + GIP + Glucagon triple agonist
Avg Weight Loss	15-20%	20-25%	25-30%+
Gray Market Availability	High	High	Limited (newer)
Forms Available	Vials, Pens	Vials, Pens	Vials only
Typical Dose Range	0.25-2.4mg/week	2.5-15mg/week	2-12mg/week

Detailed Comparisons

Mechanism of Action

How Each Medication Works

Semaglutide (GLP-1 Only)

• Mimics the GLP-1 hormone
• Slows gastric emptying
• Reduces appetite
• Improves insulin sensitivity

Tirzepatide (Dual Agonist)

• Activates both GLP-1 and GIP receptors
• Enhanced glucose control
• Greater appetite suppression
• Improved metabolic effects

Retatrutide (Triple Agonist)

• Activates GLP-1, GIP, and glucagon receptors
• Maximum metabolic activation
• Increased energy expenditure
• Most comprehensive appetite control
• Enhanced fat burning through glucagon activation

Efficacy & Results

Weight Loss Outcomes

Semaglutide

• Clinical trials: 15-20% body weight reduction
• Timeline: Full effects in 3-4 months
• Plateau: Common around 6-9 months

Tirzepatide

• Clinical trials: 20-25% body weight reduction
• Timeline: Full effects in 4-5 months
• Plateau: Less pronounced than semaglutide

Retatrutide

• Clinical trials: 25-30%+ body weight reduction
• Timeline: Full effects in 4-6 months
• Plateau: Still being studied
• Note: Phase 2 data shows promise for >30% weight loss in some patients

Dosing Protocols

Standard Dosing Schedules

Semaglutide

Week 1-4: 0.25mg weekly
Week 5-8: 0.5mg weekly
Week 9-12: 1mg weekly
Week 13+: 1.7-2.4mg weekly (if tolerated)

Tirzepatide

Week 1-4: 2.5mg weekly
Week 5-8: 5mg weekly
Week 9-12: 7.5mg weekly
Week 13-16: 10mg weekly
Week 17+: 12.5-15mg weekly (if needed)

Retatrutide

Week 1-4: 2mg weekly
Week 5-8: 4mg weekly
Week 9-12: 6mg weekly
Week 13-16: 8mg weekly
Week 17+: 10-12mg weekly (if tolerated)

Side Effects

Common Side Effects by Medication

All Three Medications Share:

• Nausea (most common)
• Vomiting
• Diarrhea
• Constipation
• Abdominal pain
• Decreased appetite

Severity Patterns:

• Semaglutide: Generally well-tolerated after adjustment period
• Tirzepatide: Similar to semaglutide, possibly fewer GI issues
• Retatrutide: May have more initial side effects due to triple action

Managing Side Effects:

1. Start with lowest dose
2. Increase slowly (every 4 weeks)
3. Take with food if needed
4. Stay hydrated
5. Consider anti-nausea medication

Gray Market Availability

Sourcing Considerations

Semaglutide

• Most widely available
• Many verified vendors
• Consistent quality from established sources
• Available as both vials and pre-filled pens

Tirzepatide

• Good availability
• Growing number of vendors
• Quality improving as production scales
• Mostly vials, some pens emerging

Retatrutide

• Limited availability (newer compound)
• Fewer verified vendors
• Quality varies significantly
• Vials only currently
• Higher price due to limited supply
• Recommend Janoshik testing for verification

Which One Should You Choose?

Consider Semaglutide If:

• You're new to GLP-1 medications
• You want the most established option
• You prefer maximum vendor choice
• You're sensitive to side effects

Consider Tirzepatide If:

• You want enhanced weight loss over semaglutide
• You've plateaued on semaglutide
• You want good availability with better efficacy
• You can handle slightly more complex dosing

Consider Retatrutide If:

• You want maximum weight loss potential
• You're comfortable with newer medications
• You can source from verified vendors
• You're willing to pay premium prices
• You're comfortable with potential for more side effects

Important Safety Notes

warning

All three medications require:

• Medical supervision
• Regular monitoring
• Proper storage and handling
• Gradual dose escalation
• Attention to side effects

info

Retatrutide is the newest option and has less long-term safety data compared to semaglutide and tirzepatide. Consider this when making your decision.

Frequently Asked Questions

Next Steps

1. Review the dosing principles for safe usage
2. Check verified vendors for availability
3. Consider starting with semaglutide if you're new to these medications
4. Consult with a healthcare provider when possible

Remember: The "best" medication is the one you can access reliably, tolerate well, and use consistently.

By Mr Fox

Published April 17, 2025